title: Wild-type distributions of seven oral second-line drugs against Mycobacterium tuberculosis.
abstract: OBJECTIVE
  To determine wild-type minimum inhibitory concentration (MIC) distributions for Mycobacterium tuberculosis, as the background data for defining susceptibility breakpoints are limited.
  
  
  METHODS
  We determined wild-type MIC distributions of M. tuberculosis using a 96-stick replicator in Middlebrook 7H10 (7H10) medium for ethionamide (ETH), prothionamide, thiacetazone, cycloserine, rifabutin (RFB), clofazimine and linezolid in consecutive susceptible clinical isolates (n = 78).
  
  
  RESULTS
  Tentative epidemiological wild-type cut-offs (ECOFF) were determined for all investigated drugs where World Health Organization recommended critical concentrations for 7H10 are lacking, except for ETH. As the ECOFF was closely related to the non-wild-type strains for ETH and thiacetazone, the use of an intermediary (I) category in drug susceptibility testing could increase reproducibility. The cross-resistance between ETH and isoniazid was 21%. Applying 0.5 mg/l as a breakpoint for RFB classified two non-wild type and rpoB mutated isolates as susceptible for RFB and resistant against rifampicin.
  
  
  CONCLUSIONS
  We propose that wild-type MIC distributions should be used as a tool to define clinical breakpoints against second-line drugs. This is increasingly important considering the rapid emergence of drug resistance.
authors.affiliation: Department of Clinical Microbiology, Kalmar County Hospital, Kalmar, Sweden. thomassc@ltkalmar.se
authors.forename: T
authors.initials: T
authors.lastname: Schön
authors.forename: P
authors.initials: P
authors.lastname: Juréen
authors.forename: E
authors.initials: E
authors.lastname: Chryssanthou
authors.forename: C G
authors.initials: CG
authors.lastname: Giske
authors.forename: E
authors.initials: E
authors.lastname: Sturegård
authors.forename: G
authors.initials: G
authors.lastname: Kahlmeter
authors.forename: S
authors.initials: S
authors.lastname: Hoffner
authors.forename: K A
authors.initials: KA
authors.lastname: Angeby
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D015203:Reproducibility of Results; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000382:microbiology; D014944:World Health Organization
chemical_list: D000995:Antitubercular Agents